Radioactive iodinated (i131) fatty material admixed with wax-like material in capsule



RADIOACTIVE IQDINATED (I FATTY MATE- RIAL ADMIXED WITH WAX-LIKE MATERIAL IN CAPSULE Paul Numerof, Highland Park, N.J., and Joseph Knoll,

Springfield Gardens, N.Y., assignors to Olin Mathieso n Chemical Corporation, New York, N.Y., a corporation of Virginia N Drawing. Filed Aug. 1, 1958, Ser. No. 752,398

10 Claims. (Cl. 167-51) This invention relates to radioactive pharmaceutical preparations and, more particularly, to stable preparations of radioactive fatty materials for diagnostic purposes.

It is frequently desirable that means be provided for tracing the course of aparticular medicament or diagnostic agent in the system of the patient undergoing treatment. One technique which has been employed widely in the last several years makes use of the properties of radioactive substances in order to achieve this objective. In particular, radioactive fatty materials have been employed in order to faciltate the study of pancreatic function and gastrointestinal absorption. However, the liquid radiopharmaceutical preparations heretofore available have suffered from certain disadvantages, primarily from difliculties in handling and in administration inherent in the use of a liquid preparation. There is, therefore, a continued demand for the development of radio-active pharmaceutical preparations in a form which is easier to standardize and handle and which is simpler to administer.

It is an object of the present invention to provide readily administrable radiopharmaceutical preparations.

It is a more particular object of this invention to provide readily administrable preparations of radioactive fatty materials.

Other objects of this invention will in part be obvious and will in part appear hereinafter.

It has been found that the above and other objects can be achieved by the provision of the noval formulations of the present invention, which are radiopharmaceutical preparations comprising an intimate admixture of a radioactive-iodinated, normally liquid fatty material and a waxlike material having a softening point at least above room temperature. The preparations are preferably contained in an encapsuling substance of the type conventionally employed in capsules. The term fatty material as employed herein includes fatty acids and fats.

The compositions of the present invention afford a product containing the radioactive fatty material in a form which is easier and simpler to standardize and to handle than heretofore available. More particularly, the products of the present invention contain the radioactive fatty materials in a form which provides for far greater ease of administration and also of calibration. It has been found that the radio-pharmaceutical preparations of the present invention are easier for the physician to handle and to administer. In addition, it has been found that loss of radioactivity and leakage of the carrier from the container are both prevented by the present invention.

The radioactive fatty material employed in the compositions of the present invention can be any one of the radioactive fats and fatty acids now employed in therapeutic or diagnostic applications. More particularly, these radioactive fatty materials are liquids which are derived from unsaturated fatty substances which are capable of combining with molecular iodine to form iodinated fats. Representative of such unsaturated fatty materials are glycerides of unsaturated fatty acids, such as triolein, the triglyceride of oleic acid, and unsaturated fatty acids containing one or more unsaturated carbon to carbon linkages in the fatty acid chains. Specific examples of such 3,061,510 Patented Oct. 30, 1962 fatty acids are oleic, linoleic, linolenic, and arachidonic acids.

The preparation of iodinated fatty materials containing radioactive I is well known. However, for the sake of completeness, reference is here made to the article by J. R. Malin, in Proceedings of Society for Experimental Biology and Medicine (1956), volume 92, page 471, wherein the preparations of such substances is described.

The normally solid wax-like material employed in preparing the products of the present invention can be any digestible, non-toxic material which has a softening point above room temperature. It can be selected from glycerides and other fatty acid esters, fatty acids, or vegetable Waxes which have a softening point above room temperature. Among such materials there may be mentioned hydrogenated fats and oils such as cocoanut oil, cottonseed oil, and soybean oil; saturated fatty acids suchas stearic acid, palmitic acid, and lauric acid; and vegetable waxes such as carnauba wax and ouricury wax. The normally solid wax-like material may amount to from about 50% to about 99.9% of the fat composition. Preferably, however, it will comprise about 70% of the combined weights of the radioactive fatty material and the carrier.

The preparations of this invention are preferably contained in capsules of encapsulating material which may be any substance commonly employed in the art for this purpose. In general, it has been found that gelatin capsules are the most suitable for use in the present invention.

The novel products of the present invention are readily prepared by melting the normally solid wax-like material and admixing therewith the normally liquid radioactive fatty material. Thereafter, the liquid mixture which is formed is metered into a capsule and allowed to solidify. The particular order of addition of molten wax-like material to normally liquid radioactive fatty material is not critical and either one may be admixed with the other ingredient. The capsules are preferably prepared to contain on the order of about 0.001 to about 0.200 gram of radioactive fatty material.

While in general, as stated heretofore, the normally solid Wax-like material may comprise from about 50% to about 99.9% of the total weight, it has been found that where an iodinated oleic acid is employed as the radioactive fatty material the percentage of oleic acid in the total composition should preferably not exceed 35%. If proportions of oleic acid in excess of 35% are employed it has been found that leakage of the material from the gelatin capsules will occur.

For a fuller understanding of the present invention reference is made to the following examples, which are for illustration only and are not to be construed as limiting the scope of the present invention.

Example I Three parts of hydrogenated cottonseed oil is heated to about C. and to the molten fat there is then added one part of radioactive (I iodinated oleic acid. The molten mixture is then metered into gelatin capsules and allowed to solidify. solidification of the melt occurs at 30 C. The capsules are then closed and stored in contact with the atmosphere at ambient temperature. The capsules proved stable for periods in excess of one month.

Example II The procedure of Example I is repeated using radioactive, iodinated material derived from triolein in place of the oleic acid employed in Example I. Similar satisfactory results were obtained.

The preparations of the foregoing examples are particularly designed for the clinical evaluation of gastrointestinal absorption of fats and pancreatic function, and

for this purpose are administered at dosage levels of about 10 to 100 microcuries.

The invention may be variously otherwise embodied within the scope of the appended claims.

What is claimed is:

1. A pharmaceutical preparation comprising a twopiece capsule containing an intimate admixture of from about 50% to about 99.9% of a digestible, non-toxic wax-like material having a softening point at least above room temperature, and from about 0.1% to about 50% of a normally liquid radioactive iodinated (1 fatty material.

2. The pharmaceutical preparation of claim 1 in which the wax-like material is a saturated fatty acid.

3. The pharmaceutical preparation of claim 1 in which the wax-like material is a vegetable wax.

4. The pharmaceutical preparation of claim 1 in which the radioactive fatty material is radioactive (I iodinated triolein.

5. The pharmaceutical preparation of claim 1 in which 20 the wax-like material is a hydrogenated glyceride oil.

6. The pharmaceutical preparation of claim 5 in which 'the wax-like material is a hydrogenated cottonseed oil.

7. The pharmaceutical preparation of claim 1 in which the radioactive fatty material is derived from an unsaturated fatty acid.

8. The pharmaceutical preparation of claim 7 in which the radioactive fatty material is radioactive (I iodinated oleic acid.

9. A pharmaceutical preparation comprising a twopiece capsule containing an intimate admixture of from about 65% to about 99.9% by weight of hydrogenated cottonseed oil and from about to about 0.1% of radioactive (I iodinated oleic acid.

10. The composition of claim 9 in which the capsule is a gelatin capsule.

References Cited in the file of this patent UNITED STATES PATENTS 2,298,122 Hailer Oct; 6, 1942 2,487,336 Hinds Nov. 8, 1949 2,566,200 Hicky Aug. 28, 1951 2,719,103 Jurist Sept. 27, 1955 2,844,512 Eble July 22, 1958 2,911,338 Tabern Nov. 3, 1959 OTHER REFERENCES Scope Weekly, June 6, 1956, p. 11. JAPhA, Practical Pharmacy Edition, August 1956, p. 539. 

1. A PHARMACEUTICAL PREPARATION COMPRISING A TWOPIECE CAPSULE CONTAINING AN INTIMATE ADMIXTURE OF FROM ABOUT 50% TO ABOUT 99.9% OF A DIGESTIBLE, NON-TOXIC WAX-LIKE MATERIAL HAVING A SOFTENING POINT AT LEAST ABOVE ROOM TEMPERATURE, AND FROM ABOUT 0.1% TO ABOUT 50% OF A NORMALLY LIQUID RADIOACTIVE IODINATED (I131) FATTY MATERIAL. 